This article was last reviewed on
This article waslast modified on 10 July 2017.

Patients who complain of severe chest pain are usually admitted to hospital, but between 60 and 80 percent have not had a heart attack.  Although an electrocardiogram (ECG) can help make the diagnosis, it cannot exclude it. For a firm diagnosis doctors rely on blood tests for cardiac troponins, proteins that are released from damaged heart muscle. Older tests used to take six to twelve hours or longer to detect  troponin in the blood following a heart attack. In recent years sensitive troponin tests that can measure low levels reproducibly have been developed so that an upper normal limit can be determined and increasing values can be used to make a diagnosis more quickly. However, to rule out a heart attack confidently and allow safe discharge from hospital, blood tests taken over some hours have still been needed.

An evaluation of four of the new sensitive troponin tests published in the 27 August 2009 issue of the New England Journal of Medicine was carried out on stored blood samples. The authors noted that their results suggested the possibility that a heart attack could be ruled out reliably in many patients on the basis of an undetectable first measurement, but that clinical studies were needed.

Such a "rule out" study in clinical practice was included in a report by Dr Rick Body and colleagues from Manchester, UK and Rochester, Minnesota, USA published in the 20 September 2011 issue of the Journal of the American College of Cardiology. Doctors at Manchester Royal Infirmary were asked to take a blood sample for high-sensitivity cardiac troponin T (hs-cTnT) from patients with chest pain when they arrived in the emergency department, and to take another sample more than 12 hours later.

During the next three months 915 patients had at least two tests. Of the 160 patients who had undetectable  hs-cTnT on admission, only one (0.6%) had a subsequent rise to a level diagnostic of a heart attack. His blood had been taken within an hour of the onset of chest pain. The authors suggested that in patients who are seen so early it might be prudent to repeat the test after one or two hours, and that this strategy needed formal evaluation. A potential problem with relying on a single troponin test is that patients whose blood carries an antibody to troponin can have misleadingly low test results.

In the UK study, an undetectable troponin level was found in less than 20% of the 915 patients studied. Two recent research reports from Germany suggest that the proportion of patients who have a heart attack ruled out could be increased by measuring two different proteins in the first blood sample. In addition to hs-cTnT, both groups measured copeptin, a hormone that increases rapidly in the blood in response to any stress, for example an injury or an acute infection. (This test is likely to be increased in patients with a heart attack even if their blood carries an antibody interfering with troponin measurement.) The first report was published in Clinical Chemistry online on 1 August 2011 and in print on 1 October 2011; the second in Vascular Health and Risk Management online on 19 August 2011.  Both used the criteria of normal (not necessarily undetectable) hs-cTnT and normal copeptin values in the first blood sample taken in hospital. The first group were able to rule out a heart attack in 41% of 207 patients, the second in 32% of 142 patients.

Rapid "rule out" blood tests appear to hold great promise of improving the quality of care of many patients, making hospital admission unnecessary and allowing early discharge from the emergency department. The UK National Institute for Health and Clinical Excellence (NICE) has recommended further research on the addition of copeptin to hs-cTnT in the UK clinical setting, and will issue guidance when new and substantive evidence has become available.